Discovery of predictive biomarkers for molecular target drug effectiveness of advanced colorectal cancer using phosphoproteomics

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For practice of personalized medicine, prediction of molecular target drug effectiveness and selection of sensitive patients to the drug are needed. Effect of drug depends on the activity of growth signals in which the drug is involved. Protein phosphorylation plays a crucial role for the activity of growth signals.We aimed at establishment of comprehensive quantitation method for phosphoproteins and discovery of predictive biomarkers for molecular target drug effectiveness of advanced colorectal cancer using the method. We modified previous phosphoproteomics technologies and succeeded in identification of 30000 phosphopeptides in one experiment. This is the largest study of phosphoproteomics identification to date. We also showed that activity of PDPK1 kinase, a kinase downstream of EGFR signaling pathway, might be involved in sensitivity of an anti-EGFR antibody drug Cetuximab.